US008435568B2

(12) United States Patent (10) Patent N0.: US 8,435,568 B2

Brosz et al. (45) Date of Patent: *May 7, 2013

(54) USE OF WF10 FOR TREATING ALLERGIC (56) References Cited

ASTHMA, ALLERGIC RHINITIS AND
ATOPIC DERMATITIS U.S. PATENT DOCUMENTS
4,507,285 A 3/1985 Kuehne
(75) Inventors: Mathias Brosz, WanZleben-Blumenberg 4,574,084 A 3/1986 Berger
(DE); Friedrich-Wilhelm Kuhne, . - - , ,
2 Euehh?e 31
ue e et .

wanzleben (DE), Klaus BlaszkleWItz, 5,384,134 A 1/1995 Kross et al‘

Heldelberg (DE), Thomas Isensee, 5 877 222 A 3/1999 MCGrath
SulZeIal (DE) 6,703,202 B2 3/2004 McGrath et a1.
8,252,343 B2 * 8/2012 Brosz et a1. ................. .. 424/661
(73) Assignee: Nuvo Research AG, Fribourg (CH) 2005/0129784 A1 * 6/2005 Kuehne et a1. .............. .. 424/661
2007/0145328 A1 6/2007 Boulanger et a1.
* ' . ~ ~ ~ ~ 2009/0004295 A1 1/2009 Kuehne et al.
( ) Notlce. Subject to any d1scla1mer, the term ofthis 2011/0076344 A1 3/2011 Kuehne et 31‘
patent is extended or adjusted under 35
U.S.C. 154(b) by 0 days. FOREIGN PATENT DOCUMENTS
This patent is subject to a terminal dis- CA 1174976 A * 9/1984
laimer EP 0 200 156 B1 11/1986
C ' EP 0 200157 B1 11/1986
EP 0 561 145 B1 9/1993
(21) Appl- NO-I 13/560,032 JP 60-500572 4/1985
JP 9-511752 11/1997
(22) Filed; Jul, 27, 2012 W0 WO 96/28173 9/1996
(65) Prior Publication Data OTHER PUBLICATIONS
Us 2012/0294849 A1 NOV' 22’ 2012 Of?ce Action issued on Oct. 6, 2011 by the Examiner in US. Appl.
No. 12/894,618 (US 2011/0076344).
Related US. Application Data _
_ _ _ _ (Contlnued)
(63) Contlnuation of appllcation No. 12/602,589, ?led as
application No. PCT/EP2008/004312 on May 30, Primary Examiner i Bethany Barham
2008’ HOW Pat' NO' 8’252’ 343' (74) Attorney, Agent, or Firm * Foley & Lardner LLP
(60) Provisional application No. 60/941,438, ?led on Jun.
1’ 2007_ (57) ABSTRACT
The present invention provides a method of treating or inhib
(51) Int“ Cl“ iting at least one of allergic asthma, allergic rhinitis and atopic
A01N 59/08 (2006-01) dermatitis, or of reducing, inhibiting or treating allergy like
(52) U-s- Cl- symptoms. The methods use compositions comprising chlo
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. rite, chloride, chlorate and/0r sulfate ions'

(58) Field of Classi?cation Search ...................... .. None

See application ?le for complete search history. 20 Claims, 1 Drawing Sheet

WF10 Rx Pharmacodynamics: Systemic Allergy

8000

n.-1

_5 6000 lL-B
3
9.’
a. TNF-a
Lu
0
5 4°00 IP10
Q
0
% MIP-1a
a
m 2000

Day after WF10 Rx

 US 8,435,568 B2
Page 2
OTHER PUBLICATIONS
International Search Report issued on Sep. 12, 2008 in US. Appl. No.
PCT/EP2008/004312.
Habermann et al., “Oxoferin and sodium chloriteia comparison,”
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Levo et al., “Correlation between anti-DNA antibody titre and psy
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Kodelja et al.; “Alternative Macrophage Activation-Assoc ated CC
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Stein et al.; “Interleukin 4 Potently Enhances Murine Macrophage
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Fagnoni et al.; “Role of B70/B7-2 in DC4+ T-Cell Immune
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Rudd; “Upstream-Downstream: CD28 Cosignaling Pathway and T
Cell Function” Immunity; vol. 4; Jun. 1996; 527-534.
Yokose et al.; Studies of Carcinogenicity of Sodium Chlorite in
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1263-1272, 1454-1457, 1492-1507, 1509-1524, 1624-1630, 1757
1761, 2052, 2053, 2221-2223.
McGrath et al., “Effect of WF10 (TCDO) on antigen presentation”,
Transplantation Proceedings (1998), vol. 30, pp. 4200-4204.
Gillissen et al., “Increased Resistance towards Two Systemic Experi
mental Infections by Tetrachlorodecaoxygen Anion Complex,”
Arzneim.-Forsch./Drug Res. vol. 36(III), No. 12, pp. 1778-1782,
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Schubert et al., “The In?uence of Aciclovir, Imipenem and
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Bartkowski et al., “Effects of tetrachlorodecaxodie in a metastasiZing
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Oncol, vol. 114, Supp, S162, 1988.
Kempf et al., “Comparative Study on the Effects of Chlorite Oxygen
Reaction Product TCDO (Tetrachlorodecaoxygen) and Sodium
Chlorite Solution (NaClOZ) with Equimolar Chlorite Content on
Bone Marrow and Peripheral Blood of BDIX Rats,” Drugs Under
Experimental and Clinical Research (1993), vol. 19, No. 4, pp. 165
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Esltner E.F., “Induction of Oxidative Processes by
Tetrachlorodecaoxide,” Klin. Wochenschr., Dec. 15, 1991:69:p. 949
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Busch et al., Treatment of HIV-Infected Patients with Advanced
Symptomatic Disease with WF10 Solution (TCDO), In. Conf. Aids.,
Aug. 7-12, 1994; (10)(1) p. 204, Abst. #PB0245.
Cotran et al., “Malignant Lymphomas,” Chapter 14, Robbins
Pathologic Basis ofDisease (5” Ed. 1994), p. 634, 635, 643-645, 647.
Rimpler et al., “Balneozoon and hydroxan. Application of halogen
containing oxocomplexes for balneology and the swimming pool
area,” Forum Staedte-hygine, Patzer Verlag, DE, vol. 43, No. 5, Sep.
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McGrath et al., “Balanced Macrophage Activation Hypothesis: A
Biological Model for Development of Drugs Targeted at Macrophage
Functional States,” Pathobiology, vol. 67, pp. 277-281, 1999.
McGrath et al., “Development of WF10, a novel macrophage-regu
lating agent,” Curr. Opin. Investig. Drugs, vol. 3, No. 3, pp. 365-373,
Mar. 2002.
Of?ce Action issued on Apr. 30, 2012 by the Examiner in US. Appl.
No. 12/602,589 (US 2010/0233118).
Notice ofAllowance issued on Jul. 16, 2012 by the Examiner in US.
Appl. No. 12/602,589 (US 2010/0233118).
European Of?ce Action issued in application No. EP 08758884 on
Sep. 20, 2011.
* cited by examiner
US. Patent May 7, 2013 US 8,435,568 B2

WF10 Rx Phannacodynamics: Systemic Allergy

8000

---U--~ lL-1

5 6000
2O.
TNF-a

2 4000 IP10
ID
2 MlP-1a
E
,2 2000
TGF-B

Day after WF10 Rx

 US 8,435,568 B2
1 2
USE OF WF10 FOR TREATING ALLERGIC
ASTHMA, ALLERGIC RHINITIS AND
ATOPIC DERMATITIS
FIELD OF THE INVENTION
The present invention relates to a method of treating aller
gic asthma, allergic rhinitis and atopic dermatitis, more par
ticularly the present invention relates to the use of WF10 for
such treatment.
BACKGROUND OF THE INVENTION
Allergic rhinitis and allergic asthma are two closely related
diseases characterized by an inappropriate reaction of the
respiratory system to stimuli. (A. Gillission, G. Hoeffken, U.
R. Juergens: A Connection Between Allergic Rhinitis and
Allergic Asthma? The “One-Airway-One-Disease”-Hypoth
esis. Part 2: Clinical Manifestation, Diagnosis and Shared
Therapies. Pneumologe 59 (2005), 192-200). (J. Bousquet:
Allergithinitis and its Impact onAsthma (ARIA). Clinical&
Experimental Allergy Reviews 3 (1), 43-45). Data from
immunologic, genetic and epidemiologic studies point to a
systemic link between rhinitis and allergic asthma and which
can be seen as manifestations of a common atopic syndrome. 25
Often, the initial reaction of af?icted persons is allergic rhini
tis with asthma symptoms appearing years later. These aller
gic diseases can also progress to affect organs other than the
nose, throat and lungs including the eyes, skin and gas
trointestinal tract. Additional symptoms include conjunctivi
tis and other eye related symptoms including eye lid swelling
as well as skin related reactions such as atopic dermatitis and
psoriasis.
In asthma, the airways become blocked or narrowed caus
ing dif?culty breathing. Allergic asthma is characterized by
symptoms of coughing, wheeZing, shortness of breath or
rapid breathing, and chest tightness that are triggered by an
allergic reaction to inhaled allergens such as dust mite aller
gen, pet dander, pollen and mold. Symptoms in asthma
patients often can be life threatening. The strong bronchoc
onstriction and the swelling of the airways can reduce the
oxygen and CO2 exchange in the lungs to an extent where
patients die from suffocation.
Asthma in general is one of the most common chronic
diseases worldwide and a serious global health problem in
terms of health care costs and reduced quality of life. People
of all ages in countries throughout the world are affected by
this disorder although children are particularly susceptible.
According to the worldwide Global Initiative for Asthma
(GINA), as many as 300 million people worldwide suffer
from asthma and this is expected to increase by another 100
million by 2025. Allergic asthma is the most common form,
affecting over 50% of sufferers.
Rhinitis symptoms include nasal itching, sneeZing, nasal
congestion, rhinorrhea (runny nose), and postnasal drainage.
Patients with rhinitis frequently have coexisting non-nasal
symptoms as well including ocular symptoms, such as itch
ing, swelling, increased lacrimation, and redness. In addition,
patients may complain of itching of the throat, constant clear
ing of secretions from the throat, irritation of the throat,
and/ or cough. Otic symptoms can include decreased hearing,
popping, and fullness. When nasal symptoms are severe, they
may be accompanied by itching in the ears and/or palate.
There may be interference with aeration and drainage of the
paranasal sinuses, resulting in headache or facial pressure or
pain. In addition, systemic symptoms, including weakness,
malaise, fatigue, poor appetite, and cognitive impairment,
have been associated with rhinitis. Allergic rhinitis is not
life-threatening, as is allergic asthma, but it can have a sig
ni?cant impact on quality of life.
Generally the treatment of asthmatic patients focuses on
measurements of asthma symptoms, sleep disturbance, use of
rescue medication, limitations of daily activity, lung function
as well as patient and physician assessments. The goal of
asthma treatment is well-controlled asthma which is gener
ally regarded as including: symptoms occurring twice per
week or less, use of a rescue bronchodilator twice a week or
less, no nighttime or early morning awakening, no limitations
on exercise work or school, normal peak expiratory ?ow
(PEF) or forced expiratory volume (FEV), Complete or total
control of asthma symptoms includes: no asthma symptoms
and no rescue bronchodilator use as well as no nighttime or
early morning awakening and no limitations on exercise,
work or school. Well-controlled asthma is generally a realistic
target for most but not all patients. Some patients may wish to
20 achieve complete control. However, some may only be able to
achieve well-controlled or completely controlled asthma with
medications or doses of medications that cause signi?cant
adverse effects. There are also certain patients that can only
achieve partial control, for example those with steroid-resis
tant asthma. In treating allergic asthma, the prevention and
interference with life threatening bronchioconstriction epi
sodes is a prime goal (W. T. Watson, A. B. Becker, F. E.
Simpson: Treatment ofallergic rhinitis with intranasal cor
ticosteroids in patients with mild asthma: @fect on lower
30 airway responsiveness. JAllergy Clin Immunol. 91 (1993),
97-101).
Several treatment options exist for rhinitis and asthma.
However, all treatments known to date provide only symptom
modi?cation or even only acute symptom reduction without
35 interfering with the cause of the disease or the disease pro
gression. In general, treatments may be life style modi?cation
to reduce the exposure to stimuli, anti-in?ammatory medica
tion to relieve the in?ammation related symptoms, in?amma
tory mediator release inhibitors to reduce the effect of single
40 mediators such as histamine or individual interleukins, symp
tomatic relievers such as anticongestants or bronchodilating
agents and ?nally immune globulins to reduce the immune
globulin E driven reaction. With the exception of immune
globulin E treatment, the options for achieving control of
45 asthma symptoms require the repeated (daily) prophylactic or
metaphylactic administration of drugs. The immune globulin
E treatment is the one exception in that it may be administered
every few months. There are no treatment options that control
the appearance of asthma symptoms for a period of l or 2
50 years.
The complicated combination of chronic medications to
reduce the frequency and severity of attacks with short acting
inhaled drugs to reduce symptoms during an attack makes
clear that current treatments are not optimal. Undesirable
55 drun related side effects arise from the use of steroids and beta
agonists. The treatment to reduce immune globulin E anti
bodies is a useful improvement but the intervention must be
repeated every few months. As well with the use of antibodies
in general, the likelihood is high that the body will identify the
60 administered antibodies as foreign and develops neutraliZing
antibodies in response. Furthermore, the current treatments
focus on the treatment of symptoms but not of the disease or
the cause of the disease. Currently there are no treatments
available that prevent the allergic reaction from occurring in
65 response to allergen exposure.
There is thus a medical need to have improved treatments
for rhinitis, asthma and atopic diseases such as atopic derma
 US 8,435,568 B2
3 4
titis. A therapy that reduces the requirement for daily treat
ments would be a substantial improvement.
SUMMARY OF THE INVENTION
In one aspect the present invention provides a method of
treating allergic asthma, allergic rhinitis and atopic dermatitis
using WF10. Further the present invention provides the use of
WF10 for such treatment.
In an alternative aspect the present invention provides a
method respective the use of WF10 for the reduction, preven
tion or treatment of allergy like symptoms comprising admin
istering to a patient suffering from allergy like symptoms a
therapeutically effective amount of WF10.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be described in further detail
below with reference to the accompanying drawing in which:
FIG. 1 is a graph showing blood analysis of gene expres
sion in patient number one relative to days post WF10 treat
ment.
DETAILED DESCRIPTION OF THE INVENTION
WF10 is a sterile, pyrogen-free, 10% (w/v) aqueous dilute
solution of the drug substance OXO-K993, which is analyti
cally characterized as a solution containing the ions chlorite
(425%), chloride (2.0%), chlorate (1.5%), sulfate (0.7%), and
sodium (4.0%). Human clinical studies have generated sub
stantial evidence of safety when WF10 is infused in a dose of
0.5 mL/kg per day for 5 consecutive days followed by a
16-day drug-free interval, constituting a “cycle”. In two pro
tocols, patients received 6 cycles of therapy and in another
trial, patients received 4 cycles followed by maintenance use
every 6 weeks for up to 128 weeks. In every case, WF10
showed an excellent safety pro?le with no steroid like side
effects, no immune suppression, no antihistamine like side
effects and no cardiovascular side effects.
WF10 has been shown to have an impact on macrophage
function (M. S. McGrath, C. Benike, F. W. Kuehne, E. Engle
mann: Eject of WF10 (TCDO) on antigen presentation.
Transplant Proc. 30 (1998), 4200-4202) by stimulating
phagocytosis and reducing the in?ammatory phenotype (M.
S. McGrath, V. Kodelja: Balanced Macrophage Activation
Hypothesis: A Biological Model for Development of Drugs
Targeted at Macrophage Functional States. Pathobiology 67
(1999), 277-281). The evidence suggests that WF10 might
down regulate immunologic activation through removal of
the in?uence of in?ammatory macrophages on chronic T cell
activation.
However, no steroid like immune-suppressive effect and
no anti-histamine like effect have been observed in studies on
WF10. Rather an immune system normalization effect has
been observed in vitro studies (M. S. McGrath, J. O. Kahn, B.
G. Hemdier. Development of WF10, a novel macrophage
regulating agent. Curr. Opin. Investig. Drugs 3 (2002), 365
373).
Macrophage function has not been reported to play any key
role in symptom expression of allergic rhinitis, asthma or any
other atopic disease.
The present invention provides a method of respective the
use of WF10 for inhibiting at least one of allergic asthma,
allergic rhinitis and atopic dermatitis comprising administer
ing to a subject suffering from at least one of allergic asthma,
allergic rhinitis and atopic dermatitis a therapeutically effec
tive amount of WF10.
The present invention also provides a method for the reduc
tion, prevention or treatment of allergy like symptoms com
prising administering to a subject suffering from allergy like
symptoms a therapeutically effective amount of WF10.
Examples of allergy like symptoms that may be reduced,
prevented or treated include, but are not limited to, allergic
rhinitis symptoms, asthma like symptoms, atopic skin reac
tions, allergic skin reactions and gastrointestinal allergen
related symptoms.
Examples of the types of symptoms described above may
include, but are not limited to, the following: symptoms that
are associated with allergic rhinitis are described in the back
ground section above and may include nasal itching, sneez
ing, nasal congestion, rhinorrhea (runny nose), and postnasal
drainage; symptoms associated with asthma may include
breathlessness, wheezing on exhale, dry cough and a feeling
of tightness in the chest; symptoms associated with atopic
skin reactions and allergic skin reactions may include scaly
20 skin, itchy skin, in?amed/ swollen skin and cracked skin; and
symptoms associated with gastrointestinal allergens may
include general discomfort, gas and bloating.
It will be understood from the description, and the
examples provided, that WF10 may be administered in symp
25 tom free patients to prevent the re-occurrence of symptoms, in
patients with mild symptoms, or even in patients with mod
erate to severe symptoms.
Patients may be drug free or drug naive, or may be receiv
ing any other anti-allergic medication in addition to WF 1 0. As
30
shown in the examples below, administration of WF 1 0 results
in a reduction of symptom expression and in a reduction of the
need for classical anti-allergic or anti-asthma medication.
WF10 is preferably administered to the subject intrave
35
nously. Especially for the inventive use WF10 may thus be
co-administered or combined with all currently known anti
allergic medication, given orally, parenterally, topically, via
transdermal therapeutic systems, rectally or by inhalation.
These medications, as mentioned above, include steroids (in
40 haled, intranasal, as eye drops, orally or via parenteral, rectal
or other routs), antihistamines, beta-agonists, anti-muscarine
drugs, immune modulators such as PDE4 inhibitors, leukot
rien antagonists, anti-IgE antibodies, and other (innovative)
medications. WF10 may also be administered as mono
45 therapy.
One embodiment of the invention is the administration of
one treatment cycle of WF10 semi-annually, annually or bi
annually. In one embodiment, a dose of 0.5 ml/kg body
weight is administered daily over 5 days as a treatment cycle
50
of infusions. In one example, WF10 is diluted for use with
normal saline or dextrose in water and is ideally used within
4 hours of preparation. Refrigerator or freezer storage is not
recommended to extend the 4-hour limit. For example, WF10
can be administered as a dose of 0.5 mL/kg of body weight,
55
diluted into at least 250 mL of normal saline and infused over
60-90 minutes. For ease of administration, a standard dose of
50 to 75 mL of WF10 may be administered to adults, regard
less of the body weight. Depending on the individual medical
60 need, the dose may be reduced to 0.375, or even 0.1 ml/kg, or
as 5 to 50 mg per individual. In young children or sensitive
persons on one hand, and in very severely affected or resistant
patients on the other hand, the dose may be further adjusted
within the range of 0.01 to 2 ml/kg. The dose adjustment is to
65 be performed according to the individual medical need and in
line with the decision of the physician prescribing the treat
ment.
 US 8,435,568 B2
5 6
In a further embodiment, the WF 1 0 has a concentration of
about 40 to about 80 mMol of ClO2 per liter. In another
embodiment, the WFlO has a concentration of about 60
mMol ClO2 per liter.
In one embodiment, an infusion pump may be used for the
administration of WFlO. In one embodiment, infusions are
administered daily on consecutive days (for example each
day for 5 consecutive days), but it is also possible to admin
ister the drug every other day or to prolong the breaks between
infusions to 2 or 3 days, accommodating weekends and holi
days without interference with the pharmacological effect. In
one embodiment, one cycle constitutes 5 infusions. However,
since good effects have been seen after 2 to 3 infusions, the
treatment may also consist of a short cycle of 2 or 3 or 4
infusions. In individual cases, a single infusion may be suf?
cient.
In one embodiment, the administration of WFlO to a sub
ject may consist of 1 to 6 daily infusions within a 7 to 28 day
period, or alternatively within a 7 to 21 day period or within
a 7 to 14 day period. In another embodiment the administra
tion of WFlO to a subject may consist of 2 to 5 daily infusions
within a 7 to 28 day period, or within a 7 to 21 day period or
within a 7 to 14 day period. Alternatively, the administration
of WFlO to a subject may consist of 3 to 5 daily infusions
within a 7 to 28 day period, or alternatively within a 7 to 21
day period or within a 7 to 14 day period. Alternatively, the
administration of WFlO to a subject may consist of 4 to 5
daily infusions within a 7 to 28 day period, or within a 7 to 21
day period or within a 7 to 14 day period.
In another embodiment, the administration of WFlO to a
subject may consist of 1 to 6 daily infusions within a 7 day
period. Alternatively, within the 7 day period, the WFlO may
be administered to the subject as 2 to 5 daily infusions or
alternatively as 3 to 5 daily infusions or 4 to 5 daily infusions.
While the cycles may be repeated as frequently as every 2
to 3 weeks, the treatment interval may be semi-annually,
annually or bi-annually. The treatment interval for each cycle
may be adjusted to meet the individual symptoms. A single
course will be suf?cient to reduce the symptoms for a pro
longed period, but in severely affected individuals, two or
three cycles spaced every 2 to 4 weeks may be necessary to
suppress or largely reduce the symptoms. As soon as a good
therapeutic effect is reached, no further cycles are needed
until re-occurrence of the symptoms which may be for one or
two years. Alternatively, to prevent the re-occurrence, the
treatment may be repeated every year or every two years, for
example, or in heavily affected individuals twice a year, or
more frequently if desired.
A treatment cycle within the above mentioned dose range
may also be made in combination with a treatment cycle of
anti-IgE (for example Omalizumab) or anti-TNFalpha anti
bodies or other anti-in?ammatory drugs to reduce the in?am
matory reaction. This may be especially needed in severely
affected individuals which are in need to remain exposed to
the allergen, such as farmers with farmer’s lung or other
employees who can not reduce the allergen exposure, or in
other individuals in need of the strongest medication avail
able.
The treatment cycles may be also combined with steroid
administration (inhaled, intranasal, topical or oral) and all
other anti-allergic or anti-asthma medication. To support the
pharmacological effect especially during the ?rst days of a
treatment cycle, the infusion therapy may be also combined
with bronchodilating agents such as beta-agonists or anti
cholinergics, with anti-congestants in patients with allergic
rhinitis, with anti-allergic eye drops, with antihistamines,
with topical creams such as topical immune modulators
(TIMS) such as pimecrolimus or tacrolimus or cyclosporine
(topical or systemically) in patients with atopic dermatitis or
psoriasis symptoms and other patients in need thereof, with
topical steroids in patients with atopic dermatitis or psoriasis.
The infusion cycles may also be combined with educational
treatment and counselling to improve the living habits and to
learn to cope with acute symptoms of asthma or other allergic
diseases and with other adj uvant treatments including but not
limited to acupuncture, acupressure, physical therapy, and,
especially in the case of atopic dermatitis or psoriasis, cos
metic therapy to improve further the quality of life and to help
reach quickly a normal symptom free living or a living at a
largely reduced symptom level.
The present invention further provides a method of reduc
ing the expression of at least one proin?ammatory agent, for
example, a cytokine and/or a chemokine, in a subject suffer
ing from allergy like symptoms. Pro-in?ammatory agents are
agents that are known to play an active role in the in?amma
tory process, such agents are documented and known in the
20 art. In one embodiment a method is provided for reducing the
expression of at least one pro-in?ammatory agent, for
example MIP- 1 a, IL-8, IL- 1, and TNF-alpha, and in particu
lar MIP-la and IL-8, in a subject suffering from allergy like
symptoms, comprising administering WFlO to the subject.
25 The administration of the WFlO, for the reduction in the
expression of at least one pro-in?ammatory agent, occurs as
described herein. For example, the administration of the
WFlO may consist of 4 daily infusions during a 6 or 7 day
period.
30 It will be understood that the present invention is directed
towards the treatment of a subject that includes mammals, for
example humans, horses, cats and dogs.
In one embodiment the present invention provides for the
use of WFlO for the prevention, metaphylaxis or treatment of
35 allergy like symptoms
In a further embodiment the present invention provides for
the use of WFlO for the prevention, metaphylaxis or treat
ment of allergy like symptoms including but not limited to
allergic rhinitis like symptoms, asthma like symptoms, atopic
40 or allergic skin reactions, or gastrointestinal allergen related
reactions in subject.
Such reactions are well known for horses where allergic
rhinitis and asthma like symptoms are very frequent and have
a huge impact on quality of life of the horse and on usability
45 for the owner. Allergens responsible for the reactions often
are found in hay, but also in bedding and food. However, cats
and dogs are also known to express allergic rhinitis or asthma
like symptoms. In dogs, the organ which reacts most fre
quently to allergens (in contrast to human beings) is the skin.
50 Dogs and often also cats develop severe atopic dermatitis or
allergic dermatitis and in both species, and other species, the
second organ which often manifests allergic reactions is the
gastrointestinal system. Indeed, allergic diarrhoea is frequent
in dogs.
55 WFlO may be infused at a dose of 0.5 ml/kg with up to 5
infusions administered in one course and with repetition of
the treatment cycles every few weeks or more likely once a
year or even less frequent, depending on the symptoms of the
animal. As with human beings, the dose and frequency of
60 administration may be adjusted according to the individual
need of the animal.
According to the present invention, and as described below,
WFlO was administered to 4 patients with allergic rhinitis,
allergic rhinitis with asthma or allergic rhinitis with asthma
65 and atopic or allergic dermatitis. All four patients had previ
ously reported a broad spectrum of allergic reaction. Two
patients had used their daily anti-allergic medication for
 US 8,435,568 B2
7 8
years. In every case, the patients had been suffering from their
individual diseases for many years and had used numerous
different drugs, with varying effect but never with full satis
faction.
In patients, suffering from their symptoms for many years,
a signi?cant clinical bene?t ofWF10 treatment was ob served.
Unexpectedly, the symptom reduction persisted for a very
long period of time after cessation of the therapy. A similar
long lasting effect on the allergic reaction, to a point where no
active drug can be found in the body, has not been reported for
any known anti-allergic drug.
The following examples serve to illustrate preferred
embodiments of the present invention. Those skilled in the art
will recognise that various modi?cations may be made to the
foregoing description and the following examples and that the
following examples are not meant to be limiting with respect
to the scope of the invention.
EXAMPLE 1
Case Report of Patient #1
A male patient (date of birth Sep. 21, 1963) presented with
allergic rhinitis and allergic bronchial asthma. Over a 25 year
period, the patient exhibited a wideband allergic reaction
each year from early February until late October with asth
matic component. During that 25 year period, additional
clinical manifestations of neurodermatitis occurred, espe
cially head, face and ?ngers with open encrusted skin areas,
painful and extreme dry skin areas, blistering skin.
Subsequent to the 25 year period mentioned above, and
during a period of extreme allergic rhinitis with bronchial
asthma, 4 daily infusions of WF10 within one week were
administered. After 10 days, the patient was symptom free for
two years after which the symptoms returned but were less
severe.
Several medications were used prior to the ?rst experience
with WF10. During 25 years different allergen-desensitiZing
therapies: oral therapy, injection cycles over 2 to 3 years
combined with permanent oral medication. Results were per
manent tiredness without signi?cant therapy effects. Excep
tion was with Kenalog (Triamcinolone intramuscular), how
ever, side effects were not acceptable.
Medications that were used included: Tavegyl (clamestin,
antihistamine), Dehistin (histamine h1 antagonists), Kenalog
(Triamcinolone intramuscular), and Intal (cromolyn sodium
inhalation aerosol).
Stop of all therapy options to treat allergic rhinitis and
bronchial asthma by the patient during the above mentioned
25 year period. In that period, topical application of corticoids
was administered because of neurodermatitis. Within this
period there were 2 episodes of prednisolon application
because of acute status of neurodermatitis.
During a 5 year period in the above mentioned 25 year
period, no other antihistamine or antiallergic medication were
administered. The only exception was an emergency aerosol
to treat acute broncial asthma.
The patient was treated with WF10 using a dose of 0.5
ml/kg body weight. WF10 was administered to the patient on
day 1. day 2, day 3, day 6. There were no measurable effects
reported by patient during treatment period.
About 10 days after start of infusions, the patient was
abruptly free of any symptoms of allergic rhinitis and asthma.
This continued through for 2 years following therapy after
which the therapy was repeated biannually with the same
doctor and the results were reproduced each time.
In addition, the patient changed their physical location to a
place which had a distinct difference in vegetation and spec
trum of allergens from the previous location. Symptoms of
allergic rhinitis and bronchial asthma were still improved
despite this change. One day was needed for acclimatization
to the new environment and thereafter the patient was symp
tom free.
Blood analysis of gene expression in patient #1 relative to
days post WF10 treatment is graphically depicted in FIG. 1.
Blood samples were taken before each treatment and analy
sed using light cycler technology. Values taken at Day 0 were
pre-WF10 treatment. Samples taken on day 1 were taken after
the ?rst infusion, samples taken on day 2 after the second
infusion and samples taken on day 6 after the fourth infusion.
As can be seen from FIG. 1 there is a signi?cant reduction in
the expression of IL-8 and MIP-1a after WF10 treatment. An
overall reduction is also seen for IL-1, TNF-(x and IP10.
20 EXAMPLE 2
Case Report of Patient #2
A female patient (date of birth Mar. 1, 1955) presented with
25 allergic rhinitis and allergic bronchial asthma. There was an
initial diagnosis of allergic rhinitis and bronchial asthma in
1996. Before 1996, the symptoms were diagnosed and treated
as colds several times per year. Symptoms between the end of
January/February and October were characterised as hay
30 fever with bouts of sneeZing (up to 20 times per bout), sore
throats, headache, in?amed eyes and ears, allergic asthma,
and neurodermatitis.
The otorhinolaryngolo gist did not recommend an allergen
desensitiZing therapy because of the wideband allergic spec
35 trum.
Medications used prior to the administration of WF10
included years of daily application within period of allergen
exposure of several prescription medications. The last ones to
be used were: Telfast (Fexofenadin), Cromo-CT eye drops
40 (Natriumcromoglicat), Vlvidrin acute nose spray (Azelastin),
Symbicord-Turbohaler and Dermatop salve (Cortison)
Antiallergic medications used within the last 3 weeks
before ?rst WF10 application included: Telfast, eye drops,
nose spray, Symbicord and Dermatop.
45 The patient was administered WF10 at a dose of 0.5 ml/kg
body weight. The application days were: 6 (1/2 dose)/7/8/ 15/
16/20 (1/2 dose) Jun., 2006.
The course of treatment and overall assessment after infu
sion on application day was as follows. On a scale ranging
50 from 1 to 6, 1 being the best and 6 the worst possible disease
rating, the patient reported the following disease seventies:
day 7iGeneral status rated 3 with additional medication as
before; day SiGeneral status rated 2 without additional
medication; day 15iSigni?cant improvement, just slight
55 medical conditions regarding throat and respiratory system,
only minor symptoms of rhinitis observed; day 16iMinor
symptoms of rhinitis decreasing, no headache, no coughing
even after high exposure to grass pollen; and day 204Overall
status rated 2, slight skin irritation at palms. Total constitution
excellent, especially in the morning without any problems
with in?amed eyes.
Overall improvement of the patient’s general condition.
Physical capacity signi?cantly improved. Drastic improve
ment recognizable after third infusion. No other medications
65 necessary with exception of Dermatop salve for topical appli
cation to skin areas with neurodermatitis. Patient continued
through summer allergy season without any other medica
 US 8,435,568 B2
tion, symptom free for the rest of 2006 and 2007. Symptoms
returned in 2008 and the patient was subsequently treated
with WF10.
Only side effect after initial WF10 treatment was slight
skin irritation at palms 10 days after infusion. Patient very
satis?ed with treatment.
EXAMPLE 3
Case Report of Patient #3
A female patient (date of birth Oct. 25, 1954) presented
with allergic rhinitis and allergic bronchial asthma. Diagnosis
of allergic rhinitis and bronchial asthma occurred in 1990.
Symptoms of allergic rhinitis and bronchial asthma charac
terized by sneeZing bouts, headache, in?amed eyes, cough,
respiratory depression as well as neurodermatitis. Symptoms
present between the end of January/February and October/
November.
Several medications were used prior to the administration
of WF 1 0. Over years, daily application within period of aller
gen exposition of several medications available only on pre
scription. The last ones included: Xusal (LevocetiriZin),
Cromo-CT eye drops (Natriumcromoglicat), Vividrin acute
nose spray (Azelastin), and Symbicord-Turbohaler.
Antiallergic medications were used within the last 3 weeks
before ?rst WF10 application and included: Xusal, eye drops,
nose spray, Symbicord (several times a day as necessary)
The patient was administered WF10 at a dose of 0.5 ml/kg
body weight. The application days were: 5/8/11/18/19 Sep.,
2006.
The course of treatment and overall assessment after infu
sion on application day was as follows. Application of any
antiallergic drug (see above) stopped before ?rst WF10 infu
sion: day 8inose itching, in?amed eyes; day 11 (without
additional medication)inose itching, in?amed eyes; day 18
(without additional medication)inose itching decreased,
eyes symptom free; and day 19 (without additional medica
tion)isymptoms further decreased. Signi?cant overall
improvement in patient’s general condition recognizable
after third infusion.
Patient was symptom free in 2006 and was very satis?ed
with treatment. The patient reported a recurrence of hay fever
symptoms in 2007 but these symptoms were milder than
those reported before the WF10 treatment. No hay fever
symptoms reported in ?rst quarter of 2008.
Main allergy season is between March and June. Prior to
WF10 therapy the patient could not go through the allergy
season without antiallergic medications.
EXAMPLE 4
Case Report of Patient #4
Patient experienced annual allergy symptoms for the past
25 years. The symptoms included excessively swollen eyes,
especially in the morning; strong itching in the eyes; continu
ously running nose; headache; and sense of fatigue (without
medication). The symptoms typically started in mid-Febru
ary at the start of hey fever season and culminated inApril and
May during the movement of birch pollen. The symptoms
usually subsided thereafter.
The patient has a known allergy to birch pollen and early
prospering plants like hazelnut and willow trees, and a known
a cross-reaction with certain kinds of apples (experiencing a
transient furry feeling in the mouth).
10
Medications until ?rst experience with WF10:
The patient has tried a variety of medications including,
eye drops, nasal sprays like cortisone, antihistamines, and
homeopathic (e. g. HT 17) and naturopathic treatments. How
ever, nothing has really helped, except the nasal cortisone
spray.
The patient received 5 daily infusions of WF10 from Feb
ruary 12 to 16.
At the start of treatment the patient had no impression of
improvement, but as the allergy season progressed, the
patient reported that the allergy symptoms were not as pro
nounced as in previous years. The patient reported a substan
tial improvement of quality of life during birch pollen move
ment. The allergy symptoms did not disappear totally, but
were considerably less obtrusive (eyes as well as nose). Fur
ther, the patient reported that symptoms such as fatigue and
headache were virtually not existent.
In summary, the patients experienced the following
20 improvement: One patient had stopped his standard daily
medication before ?rst infusion of WF10 and after the infu
sions there was no need for any additional medication. A
second patient reduced standard medication during WF10
therapy. Two patients reported overall improvement of symp
25 toms after second and third infusion, respectively. About two
weeks after ?rst infusion patients were free of symptoms
without any medication including administration of topical
steroids.
The patient with more than 30 years of disease history and
30
atopic dermatitis had been treated the ?rst time under highest
expression of symptoms of allergic rhinitis as well as allergic
asthma. One cycle of WF 1 0 resulted in a symptom free status
after about 10 days, followed by a symptom free season in 2
35
subsequent years. Thereafter, symptoms became present
again in early spring, and the therapy had been repeated with
same clinical observation and success. Meanwhile this regi
men has been applied 5 times to that patient every two years
and every time with good success.
40 It can be concluded from the above that one cycle of WF10
every one to two years can give patients suffering from dif
ferent allergic reactions including rhinitis, conjunctivitis,
asthma, atopic dermatitis and psoriasis, one to two symptom
free years. The side effect pro?le is excellent and side effects
if observed at all are related to the infusion technology but
likely not to the drug effect. No chronic side effects have been
observed.
While this invention has been described with reference to
illustrative embodiments and examples, the description is not
50
intended to be construed in a limiting sense. Thus, various
modi?cation of the illustrative embodiments, as well as other
embodiments of the invention, will be apparent to persons
skilled in the art upon reference to this description. It is
55
therefore contemplated that the appended claims will cover
any such modi?cations or embodiments. Further, all of the
claims are hereby incorporated by reference into the descrip
tion of the preferred embodiments.
Any publications, patents and patent applications referred
60 to herein are incorporated by reference in their entirety to the
same extent as if each individual publication, patent or patent
application was speci?cally and individually indicated to be
incorporated by reference in its entirety. Even it is not expres
sively stated with respect to the described embodiment, also
65 the use of WF10 for the described treatment with some or all
of the further features described in connection with the treat
ment is subject of the present invention.
 US 8,435,568 B2
11
Further, the described use of WF10 should also comprise
the use of WF10 in the manufacture or preparation of a
medicament for the treatment described in the present appli
cation.
What is claimed is:
1. A method of treating or inhibiting at least one of allergic
asthma, allergic rhinitis and atopic dermatitis or reducing,
inhibiting or treating allergy-like symptoms in a subject suf
fering from allergy-like symptoms, wherein the allergy-like
symptoms are selected from the group consisting of:
allergic rhinitis symptoms selected from the group consist
ing of nasal itching, sneeZing, nasal congestion, rhinor
rhea, postnasal drainage, throat itching, constant clear
ing of secretions from the throat, throat irritations,
cough, ear itching, palate itching, headache, facial pres
sure, facial pain, ocular symptoms selected from the
group consisting of itching, swelling, increased lacrima
tion and redness, otic symptoms selected from the group
consisting of decreased hearing, popping and fullness,
20
and systemic symptoms selected from the group consist
ing of weakness, malaise, fatigue, poor appetite and
cognitive impairment;
asthma-like symptoms selected from coughing, wheeZing,
shortness of breath, and chest tightness;
25
atopic skin reactions and allergic skin reactions selected
from scaly skin, itchy skin, in?amed skin, swollen skin
and cracked skin; and
gastrointestinal allergen related symptoms selected from
general discomfort, gas and bloating,
30
the method comprising administering to the subject a thera
peutically effective amount of a pharmaceutical composition
comprising chlorite, chloride, chlorate and/or sulfate ions,
wherein the treatment is effected not more than once every 6
months, once every year, or once every two years.
35
2. The method of claim 1, wherein the pharmaceutical
composition comprises chlorite (C10231 ).
3. The method of claim 2, wherein the pharmaceutical
composition comprises about 40 to about 80 mMol C10; per
liter.
40
4. The method of claim 2, wherein the pharmaceutical
composition comprises about 60 mMol C10231 per liter.
5. The method of claim 2, wherein the pharmaceutical
composition further comprises chlorate.
6. The method of claim 1, wherein the pharmaceutical
45
composition comprises WF10.
7. The method of claim 1, wherein the pharmaceutical
composition consists of WF10.
8. The method of claim 1, wherein the pharmaceutical
composition is administered in a range from about 0.01 ml/kg
to 2 ml/kg body weight of the subject.
12
9. The method of claim 8, wherein the pharmaceutical
composition is administered in a range from about 0.1 ml/kg
to about 1.5 ml/kg body weight of the subject.
10. The method of claim 8, wherein the pharmaceutical
composition is administered at about 0.5 ml/kg body weight
of the subject.
11. The method of claim 1, wherein the pharmaceutical
composition is administered as a treatment of 1 to 6 daily
administrations within a 7 day period.
12. The method of claim 11, wherein the pharmaceutical
composition is administered to the subject in accordance with
a treatment selected from the group consisting of (i) 1 to 6
daily infusions within a 7 day period, (ii) 2 to 5 daily infusions
within a 7 day period, (iii) 3 to 5 daily infusions within a 7 day
period, (iv) 4 to 5 daily infusions within a 7 day period, and (v)
daily for 5 consecutive days.
13. The method of claim 1, wherein the treatment is
effected not more than once every year or once every two
years.
14. The method of claim 1, further comprising administer
ing to the subject at least one agent selected from the group
consisting of anti-lgE, anti-TNFalpha antibodies, anti-in
?ammatory agents, steroids, anti-allergic agents, and anti
asthma agents.
15. The method of claim 1, wherein the subject is a mam
mal.
16. The method of claim 1, wherein the subject is a human.
17. The method of claim 1, wherein the method comprises
reducing, inhibiting or treating allergy-like symptoms.
18. The method of claim 17, wherein the allergy-like symp
toms are at least one selected from the group consisting of:
allergic rhinitis symptoms selected from the group consist
ing of nasal itching, sneeZing, nasal congestion, rhinor
rhea, postnasal drainage, throat itching, constant clear
ing of secretions from the throat, throat irritations,
cough, ear itching, palate itching, headache, facial pres
sure, facial pain, ocular symptoms selected from the
group consisting of itching, swelling, increased lacrima
tion and redness, otic symptoms selected from the group
consisting of decreased hearing, popping and fullness,
and systemic symptoms selected from the group consist
ing of weakness, malaise, fatigue, poor appetite and
cognitive impairment.
19. The method of claim 18, wherein persistence of the
allergy like symptoms is reduced for a period of time follow
ing administration of the pharmaceutical composition
selected from the group consisting of six months, one year,
and two years.
20. The method of claim 1, wherein the pharmaceutical
composition is administered intravenously.
* * * * *
 UNITED STATES PATENT AND TRADEMARK OFFICE
CERTIFICATE OF CORRECTION
PATENT NO. 2 8,435,568 B2 Page 1 ofl
APPLICATION NO. : 13/560032
DATED : May 7, 2013
INVENTOR(S) : Mathias Brosz et a1.

It is certified that error appears in the above-identi?ed patent and that said Letters Patent is hereby corrected as shown below:

In the Specification

Column 2, line 14, please delete “(FEV),” and insert -- (FEV). --.

Column 2, line 55, please delete “drun” and insert -- drug --.

Column 3, line 12, please delete “allergy like” and insert -- allergy-like --.

Column 3, line 29, please delete “(425%)” and insert -- (4.25%) --.

Column 5, line 2, please delete “C102” and insert -- C105 --.

Column 5, line 4, please delete “C102” and insert -- C105 --.

In the Claims

Column 11, Claim 2, line 37, please delete “C1O231” and insert -- C105 --.

Column 11, Claim 4, line 42, please delete “C1O231” and insert -- C105 --.

Column 12, Claim 19, line 44, please delete “allergy like” and insert -- allergy-like --.

Signed and Sealed this

Second Day of July, 2013

Teresa Stanek Rea

Acting Director 0fthe United States Patent and Trademark O?ice